China
Africa
Explore chapters and articles related to this topic
Glutamine synthetase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Congenital deficiency of glutamine synthetase was first described by Häberle and colleagues in 2005 [1, 2] in two unrelated newborn infants. Each was the product of consanguineous Turkish parents. They died at two days and four weeks of life respectively. One had micromelia and both had malformations of the brain. So, this disease can be added to those inborn errors of metabolism that express prenatally with congenital malformation syndromes. The disease can also be added to the list of rare disorders that lead to defective synthesis of an amino acid.
Consideration of Glutamine Synthetase as a Multifunctional Protein
Published in James F. Kane, Multifunctional Proteins: Catalytic/Structural and Regulatory, 2019
The other results that caused a reevaluation of the model was the demonstration that genes exist near glnA that are involved in regulation. Their presence poses the question of whether the original mutations in K. aerogenes that affected regulation lie in these genes rather than in glnA. Significant to this consideration is the finding that the fusion of the gene for β-galactosidase to the glnA control region gives a strain with β-galactosidase regulation that mimics that of glutamine synthetase, even in the absence of a glutamine synthetase. Although these results imply that the glutamine synthetase protein is not necessary for regulation, not all features have been examined.62 Clearly, the regulation of both glutamine synthetase and nitrogen utilization are complicated processes involving a variety of components. These components need to be added to the proposed models, but the question of whether the proposal that glutamine synthetase is a regulatory protein must be totally discarded is extremely difficult to answer.
Micronutrients in the Prevention and Improvement of the Standard Therapy for Alzheimer’s Disease
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Additional evidence for the increased oxidative stress in the AD brain include the following: (a) homogenates of frontal cortex from AD brains obtained at autopsy revealed a 22% higher production of free radicals and, in the presence of iron, a 50% higher production of free radicals than those from age-matched normal controls165; (b) peroxynitrite also exacerbates the pathogenesis of AD166; (c) increased neuronal nitric oxide synthase (nNOS) expression in reactive astrocytes correlated with apoptosis in hippocampal neurons of the AD brains167; (d) the activity of glutamine synthetase decreased in the AD brains166; and (e) the level of glutathione transferase is decreased in ventricular CSF and in the AD brains compared to that in the brains from age-matched controls.168 Analysis of 50 patients with AD and 100 control subjects revealed that deletion of glutathione-S-transferase T1 increased the risk of AD by 2.47 times.169 Taken together, these data strongly suggest that increased oxidative stress represents one of the major cellular defects that play an important role in the progression of AD.
Dysregulated metabolism: A friend-to-foe skewer of macrophages
Published in International Reviews of Immunology, 2023
Keywan Mortezaee, Jamal Majidpoor
Increasing the production of succinate is important for regulation of macrophage polarization. Succinate is a known regulator of pro-inflammatory responses, mediated through HIF-1α stabilization and suppression of anti-inflammatory gene expression profile. Glutamine synthetase is an enzyme related to acid-base homeostasis and nitrogen metabolism. M2 macrophages under starvation induce the activity of glutamine synthase for production of glutamine. Blockade of glutamine synthase causes M2-to-M1 skewing of macrophages and the resultant tumor regression. Incubation of M2 macrophages with the glutamine synthase inhibitor methionine sulfoximine causes succinate accumulation and increased glucose utilization, thereby promoting metabolic rewiring toward attaining M1-like phenotype. Succinate is contributed to HIF-1α stabilization, so it is expected that blockade of glutamine synthase will cause HIF-1α activation, as it is attested [84]. Due to the interference between PKM2 activity with succinate accumulation and glycolysis for M1 polarization, a suggested strategy could be targeting PKM2.
Polyphenol-rich Spondias mombin leaf extract abates cerebral ischemia/reperfusion-induced disturbed glutamate-ammonia metabolism and multiorgan toxicity in rats
Published in Biomarkers, 2023
Olubukola Benedicta Ojo, Abigail Oladunni Olajide, Grace Boluwatife Olagunju, Comfort Olowu, Sunday Solomon Josiah, Zainab Abiola Amoo, Mary Tolulope Olaleye, Afolabi Clement Akinmoladun
Glutamate regulatory enzymes modulate glutamate metabolism and play a major role in stroke outcomes by contributing to neuronal cell death and neurological deficits (Ruban et al.2020). Glutamine synthetase (GS) is a key regulator of nitrogen metabolism which catalyses the ATP-dependent condensation of glutamate with ammonia to glutamine which enters the bloodstream and is transported to the liver (Castegna and Menga 2018). GS is predominantly expressed in glutamine-consuming organs such as the brain, liver, and kidney (Hakvoort et al.2017). Glutamine, the most abundant free amino acid in the blood, is converted to glutamate in the mitochondria, which is converted back to alpha-ketoglutarate by oxidative deamination by the tricarboxylic acid cycle (TCA) for energy generation (Liang et al.2021). Glutamine is synthesised in the central nervous system (CNS) to scavenge glutamate, in the kidney to control ammonia production needed to counteract metabolic acidosis, and in the liver to detoxify ammonia to urea (Hakvoort et al.2017). A high amount of ammonia is produced by intestinal bacteria through the action of urease and the degradation of proteins and amino acids contributes to ammonia accumulation (Castegna and Menga 2018).
Irreversible hippocampal changes induced by high fructose diet in rats
Published in Nutritional Neuroscience, 2022
Juan Fierros-Campuzano, Paola Ballesteros-Zebadúa, Joaquín Manjarrez-Marmolejo, Penélope Aguilera, Mónica Méndez-Diaz, Oscar Prospero-García, Javier Franco-Pérez
GFAP upregulation is associated with inflammatory courses, and IL-1b has been recognized as an inducer of astrogliosis [48,49]. In this study, we found significant increases in both IL-1b and GFAP. Thus, the hypothesis of IL-1b-induced astrogliosis in rats subjected to a high fructose diet appears reasonable. Additionally, GS plays an essential role in the homeostasis of glutamine/glutamate and, therefore, in the glutamatergic neurotransmission. Alterations in the expression and activity of GS are associated with some brain pathologies [50]. Further studies have shown that a decrease of hippocampal GS expression is noticeable in an Alzheimer's disease mouse model [51]. We also observed that fructose intake induced a significant decrease in GS. This alteration could be indicating an imbalance of the glutamate metabolism and, consequently, the appearance of excitotoxicity processes and oxidative insults. There is evidence supporting this hypothesis because it has been reported that both short and long-term fructose diet feeding induces high levels of reactive oxygen species, lipid peroxidation, and oxidative protein dysfunction [17,18].